Benzyl 4-Hydroxybenzoate → HCID 66630110, compound

HRID 555372Notes

Reaction equation

HRID 555372 reaction equation
[OH:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:37]([O:39][C:40]([CH:42]1[CH2:47][CH2:46][CH:45](O)[CH2:44][CH2:43]1)=[O:41])[CH3:38].CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[CH2:9]([O:8][C:6](=[O:7])[C:5]1[CH:16]=[CH:17][C:2]([O:1][CH:45]2[CH2:46][CH2:47][CH:42]([C:40]([O:39][CH2:37][CH3:38])=[O:41])[CH2:43][CH2:44]2)=[CH:3][CH:4]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 7180Benzyl 4-HydroxybenzoateHCID 11776TriphenylphosphineHCID 86973Ethyl 4-hydroxycyclohexanecarboxylateHCID 5462977Diethyl azodicarboxylate

Product 1

HCID 66630110HCID 66630110, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of benzyl 4-hydroxybenzoate (50 g, 0.22 mol) and triphenylphosphine (63.2 g, 0.241 mol) dissolved in THF (800 mL) was added 4-hydroxy-cyclohexanecarboxylic acid ethyl ester (35.3 mL, 0.22 mol). The reaction mixture was cooled on an ice bath and DEAD (38 ml, 0.241 mol) was added dropwise maintaining the temperature at 0° C. The resulting mixture was allowed slowly to reach room temperature and stirred for 16 hrs. at this temperature. The volume was reduced to app. 250 mL by evaporation and to the resulting mixture was added water (500 mL) followed by extraction with DCM (3×400 mL). The combined organic phases were washed with brine (400 mL), dried (Na2SO4), filtered and the volatiles evaporated in vacuo. Crude product ˜80 g was purified on column chromatography (Flash 75) using first heptane (7.5 L) followed by a mixture of EtOAc-heptane (1:10) (5 L) and finally a mixture of EtOAc-heptane (1:6) (8 L). Combined fractions were evaporated in vacuo affording 18.1 g (22%) of 4-(4-ethoxycarbonyl-cyclohexyloxy)-benzoic acid benzyl ester as an oil.

Workup

  1. temperatureThe reaction mixture was cooled on an ice bath
  2. customto reach room temperature
  3. custom250 mL by evaporation
  4. additionto the resulting mixture was added water (500 mL)
  5. extractionfollowed by extraction with DCM (3×400 mL)
  6. washThe combined organic phases were washed with brine (400 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customthe volatiles evaporated in vacuo
  10. customCrude product ˜80 g was purified on column chromatography (Flash 75)
  11. additionfollowed by a mixture of EtOAc-heptane (1:10) (5 L)
  12. additionfinally a mixture of EtOAc-heptane (1:6) (8 L)
  13. customCombined fractions were evaporated in vacuo

Sources & evidence

ORD record
ord-6c4d406e99cc4fffbb5fb69bbee20a45
Source dataset
uspto-grants-2011_11
Patent number
US08053447B2

Reaction notes

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